The effect of progesterone on gonadotropin secretion is stimulatory or inhibitory depending on the dose of progesterone used and the time of the estrus cycle. In the castrated female rat, progesterone in the absence of estrogen does not alter gonadotropin secretion. An animal preparation has been developed in our laboratory using the castrated female rat treated with a low subphysiologic dose of estradiol in which FSH and LH secretion can be stimulated or inhibited by a single injection of progesterone depending on the dose employed. The overall objectives of this study would be to examine the role of progesterone in the modulation of gonadotropin secretion using this rat model. The studies will examine the changes in hypothalamic and serum LHRH during progesterone induced release of inhibition of gonadotropins. The pituitary estrogen receptor concentration, binding of LHRH to the pituitary and the pituitary's sensitivity to LHRH will be sought without and with estradiol and progesterone treatment. The pattern of cytoplasmic estrogen receptor dynamics in the pituitary will be examined under stimulatory and inhibitory doses of progesterone. The incorporation of tritiated nucleotides into RNA and DNA will be studied during progesterone induced surge or suppression of gonadotropin secretion in order to get a preliminary idea of changes being induced in the gonadotropes. In view of the fact that progesterone does not modify gonadotropin secretion in the castrated rat not treated with estradiol, a search will be made for newly synthesized or unmasked receptors for progesterone that may be induced by estrogen treatment. The information gained will be of considerable importance in understanding the control of gonadotropin secretion during the ovulatory process.